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Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G.

Shraddha Sharma1, Bora E Baysal1

  • 1Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, United States of America.

Peerj
|December 13, 2017
PubMed
Summary

APOBEC3A and APOBEC3G enzymes perform C-to-U RNA editing. They preferentially edit RNA substrates with specific stem-loop structures, influenced by loop size and stem stability.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • APOBEC3A (A3A) and APOBEC3G (A3G) are cytidine deaminases with known antiviral and anti-retrotransposon functions.
  • These enzymes possess a novel C-to-U RNA editing capability.
  • While they deaminate DNA at multiple TC/CC sites, their RNA editing is more restricted, often targeting single TC/CC sites.

Purpose of the Study:

  • To investigate the specific sequence and structural preferences of APOBEC3A and APOBEC3G for RNA editing.
  • To elucidate the factors governing substrate and site-specificity in A3A and A3G-mediated RNA editing.

Main Methods:

  • Site-directed mutagenesis of endogenous cellular RNA substrates.
  • Analysis of RNA editing levels in response to sequence and structural modifications.
Keywords:
APOBEC3AAPOBEC3GCytidine deaminaseRNA editingRNA secondary structure

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Main Results:

  • Both APOBEC3A and APOBEC3G exhibit a preference for RNA substrates featuring a predicted stem-loop structure.
  • The target cytosine is preferably located at the 3'-end of the RNA loop.
  • RNA editing efficiency is significantly impacted by loop size, nucleotides adjacent to the target cytosine, and stem stability.

Conclusions:

  • RNA editing by APOBEC3A and APOBEC3G is dictated by both RNA sequence and secondary structure.
  • These findings provide a mechanistic explanation for the observed substrate and site-specificity of A3A and A3G RNA editing.